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A solid-phase extraction (SPE) method for enriching and purifying estrogenic disrupting compounds (EDCs) based on the estrogen response element was established. The estrogen receptor was used for molecular recognition, as it specifically binds EDCs. An estrogen response element was used to maintain the activity of the estrogen receptor. High-performance liquid chromatography (HPLC) was used to quantify the EDCs. This method combined with HPLC was applied to detect three kinds of EDCs, such as bisphenol A (BPA), 17β-estradiol, and diethylstilbestrol in a liquid milk matrix, with recoveries of 84.1 ± 8.2% to 113.6 ± 2.9%. The limits of detection and quantification of the established method were 1 × 10-6 mg·mL−1 and 5 × 10-6 mg·mL−1. The method was further applied to analyze market samples, including liquid milk, fermented milk, and milk powder. Only BPA was detected from one brand of liquid milk and it was below the regulatory level.